To be truly groundbreaking, a biomedical discovery needs to make a difference in the real world. That’s the premise driving translational science, a field that bridges gaps between research and clinical implementation. “We want to avoid the practice of doing research just to discover things,” said Harry Selker, dean and principal investigator at Tufts Clinical and Translational Science Institute (CTSI). “Only when it gets out in the community is there any impact.”
Founded by Tufts University and Tufts Medical Center in 2008, Tufts CTSI has been a pioneer in a relatively nascent field. In addition to overseeing a graduate program, it provides support and seed funding, runs an online-learning platform, organizes an expert panel of stakeholders to guide research teams, partners with hospitals to promote multisite clinical research, and much more. And its tireless commitment to translational science is paying off: This year, Tufts CTSI earned its third Clinical and Translational Science Award (CTSA) from the National Institutes of Health, receiving a perfect score in the award’s “UL1” section (encompassing the administrative core, informatics, community and collaboration, and more).
Among sixty or so CTSA recipients in the United States, Tufts CTSI stands out. While translational science is often touted as taking discoveries from “bench to bedside”—from the laboratory to patients—CTSI pushes the adage further than most: to broad clinical practice and public policy. “We consider ourselves the extrovert CTSA,” said Selker. “We’re more public-policy oriented.” Alice Rushforth, executive director of Tufts CTSI, agreed: “We have spent a lot of time focusing on interacting with and engaging the community,” she said.
Moving forward with the new $56 million award, Tufts CTSI plans to bolster the internal and external collaboration that has long been its driving force. “We realize we are not the largest university or medical school in the nation, but we have strengths that are specific to us,” Selker said. Those strengths are fundamentally tied to partnerships—Tufts CTSI involves various stakeholders in its research, from community groups to industry to hospitals, payers, and patient advocates. “While that might mean more work initially,” Selker said, “you’ll have a more relevant, and hopefully, a more impactful outcome.”
So, what does that impact look like? Ahead, four projects fostered by Tufts CTSI display how translational science is improving medicine.
Rethinking Treatment For Knee Osteoarthritis
From celecoxib to naproxen, there are myriad drugs to treat knee osteoarthritis—but which one works best? In his Dean’s Award-winning Clinical and Translational Science graduate program doctoral thesis, Raveendhara Bannuru, SK15, considered this question in a new way. Before his work, each intervention had generally been compared against a placebo. But with guidance and mentorship from the CTSI, Bannuru applied an innovative method to compare nine different drugs against one another, ranking them by efficacy.
The result? The treatments once considered more successful and prescribed more often, turned out to be less effective. That’s because not all placebos are created equal: Bannuru found that some placebos—specifically inert topical creams and saline injections—were actually more effective than certain active oral treatments, due to varying psychological effects and patient-doctor interactions. “We answered a common question using novel methods and techniques,” said Bannuru, who is the director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center and an assistant professor of medicine. “We would not have gotten these results with a traditional, randomized-
The study, outlined in two 2015 articles in the Annals of Internal Medicine, created a buzz in the medical world; by bucking current practice, it fueled a change in perspective. “People will always strongly resist any paradigm shift,” Bannuru said, “but this study withstood that assault due to its rigor and quality.”
Combating Inequality in Breast Cancer Care
The fruits of biomedical progress don’t always extend to all patients, especially when socioeconomic disparities come into play. Case in point: Although treatments in breast cancer have improved over time, racial disparities have increased. In Boston, for example, African-American women with the disease have a mortality rate that’s 25 percent higher than the rate for white women. Launched in 2017, Translating Research into Practice (TRIP) aims to combat clinical inequality with strategies that have been shown to reduce delays in patient care, such as establishing health-care navigators for each patient. “One hypothesis is that vulnerable groups aren’t getting access to the best treatments,” said Karen Freund, vice chair for faculty affairs and quality improvement at Tufts Medical Center and a professor of medicine. “That’s why it’s so important to study this from a translational perspective, identifying places in the translational spectrum where innovations might not be reaching all people.”
TRIP is a testament to the extroverted spirit of Tufts CTSI, which is teaming up with translational science institutes at Boston University, Harvard University, and the University of Massachusetts—plus Brigham and Women’s Hospital and the Breast Cancer Equity Coalition—to put the $8.65 million NIH award to use. The goal of the project extends beyond the 1,100 Boston-area women it will help over the next five years. If the strategies are successful, they can be replicated elsewhere, Freund said, tackling other barriers to treatment for a wide range of diseases.
Considering Communication in Kidney Disease Patients
Engaging patients and communities in clinical decision-making is central to translational science—and that includes finding ways to close gaps in communication between doctors and patients. Among older patients, treatment choices can be complex, levels of individual autonomy vary, and end-of-life discussions can be difficult. In older patients with kidney disease, for example, dialysis may not always present as much benefit as conservative management, and overly aggressive interventions may be detrimental. Yet few clinicians mention the possibility of conservative management to their patients. Older patients often do not understand that dialysis is voluntary, and research has shown that they do not always feel included in the decision.
With the help of Tufts CTSI—plus a multidisciplinary team and public and private partners—co-principal investigators Keren Ladin, assistant professor of public health and community medicine and occupational therapy, and nephrologist Daniel Weiner, A94, M98, SK04, associate professor at the medical school, are exploring these issues. Their study, “Promoting Autonomy and Improving Shared Decision Making for Older Adults with Advanced Kidney Disease,” funded by the Patient-Centered Outcomes Research Institute, combines qualitative research with a randomized trial to test the comparative effectiveness of a web-based treatment decision aid. “By taking a real-world problem that arises commonly in clinic, we then apply communication science frameworks, along with social- and behavioral-science approaches to examine the comparative effectiveness of our intervention,” Ladin said. “Our study spans the translational spectrum—we’ve worked with stakeholders to develop an intervention which is now being used in widespread practice.”
Improving Identification of Genetic Disorders in Infants
As the practice of whole-genome sequencing advances, how do we maximize the impact on patients? Among newborns with genetic disorders, it’s sometimes difficult to pinpoint a conclusive diagnosis using standard testing—it can require years of exams, hospitalizations, and clinic visits. “The emotional and financial toll this takes on families, as well as the health-care system, can be staggering,” said Jill Maron, executive director of the Mother Infant Research Institute at Tufts Medical Center and a principal investigator of the clinical trial, “Precision Medicine in the Diagnosis of Genetic Disorders in Neonates.”
With an $8 million, five-year award from the NIH, Maron and coprincipal investigator Jonathan Davis, chief of the Division of Newborn Medicine at Tufts Medical Center, have initiated a national trial that will test two different approaches to genome sequencing: whole genome, and a targeted sequencing that analyzes 1,722 possible genetic disorders affecting newborns. Partnering with Tufts CTSI, the researchers will compare the two methods among 400 newborns to determine accuracy and effectiveness. The study will also consider how much money targeted sequencing could save the health care system. “Our hope is that these platforms will transform care, lower hospitalization costs, and provide families with answers much sooner,” Maron said.
Tufts may be one of the smallest universities with a Clinical and Translational Science Award from the NIH, but it’s also especially adept at securing new partnerships beyond campus. Outlined here are three examples of exciting recent collaborations.
1. Last May, Tufts CTSI announced a plan to team up with MIT’s Institute for Medical Engineering and Science to incorporate translational research into medical-device development—ultimately, the goal of the T.5 Capacity in Medical Devices initiative is to maximize patient benefit. “The collaboration gives us an opportunity to evolve in areas of medical technology and devices, as well as information technology,” said Tufts CTSI dean and principal investigator Harry Selker.
2. The Jackson Laboratory (JAX), a biomedical research institute in Bar Harbor, Maine, has driven advances in genetics and genomics. Now, thanks to a five-year collaboration, Tufts CTSI will help JAX’s immunology and oncology research incorporate the latest translational science in the areas of research ventures, training, and educational platforms; JAX will provide new methodological approaches, research tools, and resources, plus opportunities to expand research and education programs at Tufts CTSI partner institutions.
3. Tufts CTSI’s collaborative mission extends into the private sector, too. In November, it partnered with health care giant Novartis to develop activities for research and education. The company will work with Tufts CTSI’s experts on projects of shared interest, as well as provide judges for poster competitions and other events, cohost symposia on research topics, and collaborate with Tufts CTSI’s career-development programs to offer company internships.